Project Summary/Abstract The long-term goal of this technology development project is improve the rehabilitation of veterans suffering from acute and chronic lung diseases through the development of the first truly portable, biocompatible artificial lung capable of short and long term respiratory support. Current artificial lung devices have shown promise for rehabilitation from lung disease; however, significant advances in gas exchange, biocompatibility, and portability are required to fully realize their potential. The objective of the current Merit Review proposal, which is a step toward attainment of the long-term goal, is to fully characterize the ex vivo gas exchange properties and lifetimes of microfabricated artificial lungs with feature sizes and physiological properties approaching that of the human lung as a function of design parameters and biocompatible surface coatings. Thus, we expect this Merit Review study to provide the foundation for translation of this robust technology to the clinical setting. The project objectives will be achieved in three aims. In the first aim, artificial lungs with blood channel heights as small as 10 5m and gas diffusion membranes as thin as 8 5m will be constructed and tested with human whole blood in order to, for the first time, evaluate the impact of miniaturization on gas exchange efficiencies. Due to the microscale feature size of our artificial lung, and the significant potential for thrombogenesis limiting device performance, the second aim will investigate functionalization of PDMS substrates with synthetic or biological modalities that are known to improve hemocompatibility and test the functionalizations in vitro. In the third aim, the design parameters optimized in Aim 1 and the thromboresistant modification optimized in Aim 2 will be integrated to develop a surface-modified micromachined artificial lung prototype in order to improve hemocompatibility, reduce thrombosis, and increase device lifetime. The prototype will be tested ex vivo with human whole blood. The completion of these aims will result in the characterization of the performance limits of microfabricated, hemocompatible, artificial lungs with feature sizes and physiological properties that are, for the first time, approaching those in the human lung. At the conclusion of this study, we will be well positioned to translate the technology to the clinical setting through its application in specific systems targeted at veteran pulmonary rehabilitation.